Hair loss or alopecia is a common problem in both males and females regardless of their age. There are several types of hair loss, such as androgenetic alopecia, alopecia greata, telogen effluvium, hair loss due to systemic medical problems, e.g., thyroid disease, adverse drug effects and nutritional deficiency states as well as hair loss due to scalp or hair trauma, discoid lupus erythematosus, lichen planus and structural shaft abnormalities. (Hogan and Chamberlain, 2000). Of the above, androgenetic alopecia is the most common cause of hair loss, affecting about 30% of individuals who have a strong family history of hair loss. (Bergfeld, 1988). Androgenetic alopecia is caused by three interdependent factors: male hormone dihydrotestosterone (DHT), genetic disposition and advancing age. DHT causes hair follicles to degrade and further shrink in size, resulting in weak hairs. DHT also shortens the anagen phase of the hair follicle growing cycle. Over time, more hairs are shed and hairs become thinner. Possible options for the treatment of alopecia include reassurance, hair prosthesis, surgery and topical/oral medications. (Hogan & Chamberlain, 2000; Bertolino, 1993; Setty, 1970).
The most common pharmacological management of androgenetic alopecia is topical minoxidil and finasteride taken orally. The main problem with topical minoxidil therapy is patient compliance, although it has been shown to be effective in a few studies. (DeVillez et al, 1994; Trancik R J, 1998). On the other hand, oral finasteride is associated with significant adverse effects such as decreased libido, impotence and ejaculation disorders. (Chen et al, 1996).
In addition, there is a report by Goldman et al. (1996) which evaluates whether male pattern baldness is associated with a deficiency in oxygen supply to body tissue. The results indicate that penetration of oxygen was lower in the bald frontal scalp than in hair-bearing temporal scalp area. As such, good blood supply to the scalp is essential to maintain normal cycle of hair growth.
Tocotrienol, a form of vitamin E, is a potent anti-oxidant and has been found useful in combating many health problems. While there was a report of the beneficial effects of vitamin E in hair care products (Shipp, 1994), its potential in the restoration of hair in patients taking tocotrienols as a supplement has yet to be explored. Thus, the aim of the present study was to investigate the possible intervention effects on hair loss with tocotrienols.
Vitamin E consists of 8 molecules or isoforms; four of which are known as tocopherols and four of which are known as tocotrienols. Structurally, both consist of a chromanol head and a phytyl side chain. The difference between tocopherols and tocotrienols lies in the phytyl side chain. Whereas the phytyl side chain of tocopherols is fully saturated, that of the tocotrienols has three double bonds at the 3, 7 and 11 positions. Both tocopherols and tocotrienols are further designated as alpha-, beta-, gamma- and delta-isoforms depending on the number and position of the methyl groups on the chromanol ring. Thus, tocopherols and tocotrienols are distinctively different and are not derivatives of each other (Theriault et al, Clinical Biochemistry (1990) 32(5):309).
Because of the difference observed in the phytyl chain of tocopherols and tocotrienols, the two series have also been reported to possess differences in biological activities, with the tocotrienols reportedly to be superior (Qureshi et al, J Biol Chem (1986) 261:10544; Serbinova et al, Free Radic Biol Med (1991) 10:263). Moreover, the half life of tocopherols in humans has been reported to be about 20 hours while the half-life of tocotrienols was reported to be between 2–4 hours only.
Although tocopherols have been mentioned in other patents describing hair growing agents, tocopherols are not the major active ingredient but merely act as formulation aid, as mentioned in some of the patents. The patent by Kamimura (European Patent Application Number EP1232740A2) relates to a hair growing agent, comprising phosphatidic acid as an active ingredient (as claim 1). Only in the subsequent claims did the inventor mention that “A hair-growing agent comprising, as active ingredients, the phosphatidic acid, and one or more members selected from the group consisting of proanthocyanidin, tocopherol, derivatives of tocopherol, panthothenic acid . . . ”. Moreover, the above patent only mentioned tocopherol as one of the components of the invention and not tocotrienols per se. It should be emphasized that tocotrienols are distinctly different from tocopherols.
In the patent by Mitsuyama (JP2000038340), it relates to peroral hair growth stimulants containing minoxidil AND one or more compounds chosen from a group of molecules which may consist of vitamin E. The emphasis was on minoxidil and not Vitamin E although Vitamin E as a group encompasses both tocopherol and tocotrienols. Tocotrienols were not being mentioned at all for preventing hair loss as the sole active ingredient but instead vitamin E was used more as a supplement to minoxidil or as an excipient in the preparation. On the other hand, the present invention specifically relates to preparations containing tocotrienols for promoting hair growth and not in combination with other molecules.
U.S. Pat. No. 4,439,432 (Peat) relates to the use of progesterone solubilized in tocopherol for the correction of progesteron deficiency states. The tocopherol in the preparation was not indicated for the treatment of any ailments listed in the patent, which include abnormal hair growth resulting from androgen excess, but rather the tocopherol was used as a non-toxic solvent to solubilize the progesteron such that it did not crystallize out upon mixing with biological fluids. The tocopherol used in the U.S. Pat. No. 4,439,432 was not meant to exert any therapeutic action. Tocopherol in this case was used solely as an inert excipient/carrier for progesterone so that the progesterone would not crystallize out as in the case of a prior art where ethanol was used. U.S. Pat. No. 5,591,772 by Lane et al. relates to the use of novel tocotrienols and tocotrienol-like compounds as hypocholesterolemic, antithrombotic, antioxidizing, antiatherogenic, anti-inflammatory and immunoregulatory agents. It was never mentioned in the patent that tocotrienols could be used for promoting hair growth or preventing hair loss as stated in the present invention. Hence, the aim of the present study was to investigate the possible intervention effects on hair loss with tocotrienols.